The applicability of molecular descriptors for designing an electrospray ionization mass spectrometry compatible library for drug discovery

Jennifer C. Copeland, Levi J. Zehr, Ronald L. Cerny, Robert Powers

Research output: Contribution to journalArticle

5 Scopus citations


Detecting a small molecular-weight compound by electrospray ionization mass spectrometry (ESI-MS) requires the compound to obtain a charge. Factors such as gas-phase proton affinities and analyte surface activity are correlated with a positive ESI-MS response, but unfortunately it is extremely challenging to predict from a chemical structure alone if a compound is likely to yield an observable molecular-ion peak in an ESI-MS spectrum. Thus, the design of a chemical library for an ESI-MS ligand-affinity screen is particularly daunting. Only 56.9% of the compounds from our FAST-NMR functional library [1] were detectable by ESI-MS. An analysis of ∼1,600 molecular descriptors did not identify any correlation with a positive ESI-MS response that cannot be attributed to a skewed population distribution. Unfortunately, our results suggest that molecular descriptors are not a valuable approach for designing a chemical library for an MS-based ligand affinity screen.

Original languageEnglish (US)
Pages (from-to)806-815
Number of pages10
JournalCombinatorial Chemistry and High Throughput Screening
Issue number10
StatePublished - Dec 1 2012



  • Chemical library
  • Drug discovery
  • Electrospray ionization
  • Ligand-affinity screens
  • Mass spectrometer
  • Molecular descriptors

ASJC Scopus subject areas

  • Drug Discovery
  • Computer Science Applications
  • Organic Chemistry

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